P709: CLINICAL OUTCOME OF ASCIMINIB TREATMENT IN A REAL-WORLD MULTI-RESISTANT CML PATIENT POPULATION.
Authors: C. C. Kockerols, J. J. Janssen, N. M. Blijlevens, S. K. Klein, L. G. van Hussen-Daenen, G. N. van Gorkom, W. M. Smit, P. van Balen, B. J. Biemond, M. J. Cruijsen, M. F. Corsten, P. A. te Boekhorst, H. R. Koene, G. L. van Sluis, J. J. Cornelissen, P. E. Westerweel
Journal: HemaSphere (2022)

Background: Asciminib is a first-in-class STAMP (Specifically Targeting the ABL Myristoyl Pocket) tyrosine kinase inhibitor (TKI). Asciminib was found to have superior efficacy compared to bosutinib in patients (pts) intolerant or refractory to ≥2 currently registered TKI with good tolerability. While awaiting its EMA approval, asciminib is made available by Novartis to pts with high clinical need in an early access programme (EAP) in The Netherlands. Aims: We aimed to assess treatment outcomes in this nationwide patient cohort. Methods: Dutch hematologists who treated CML pts in the asciminib EAP were asked to provide clinical data of consenting pts. Pts were included if ≥18 years and treated in this asciminib EAP, thus outside clinical trials. Treatment failure was defined as progression to advanced stage disease (AP/BC), not reaching a complete cytogenetic response or BCR-ABL1 <1%IS (CCYR/MR2.0) (=primary) or losing previously achieved responses (=secondary). Event-free survival (EFS) was defined as time from asciminib start until allogeneic stem cell transplantation (SCT), progression to AP/BC or death; whatever came first. Responses were assessed with the cumulative incidence competing risk (CICR) method considering the competing event of TKI discontinuation for any cause. Results: All hematologists agreed to participate and 53 out of 56 pts from 14 medical centers consented and were included. Most pts (72%) had been exposed to ≥3 TKIs prior to asciminib. The majority (79%) started with asciminib because of multi-resistance (with or without intolerance) including 15 pts with primary ponatinib-failure, 15 pts harboring the T315I mutation and 3 pts with compound mutations. Two pts were treated with asciminib post-SCT and were excluded from response analyses. Median asciminib exposure was 7 months (IQR 3-16). Frequently reported adverse events (AE) were cytopenia and folliculitis, classified as probably related to asciminib and manageable generally without dose modification. Only one pt definitely discontinued asciminib due to persistent anemia, but in the context of also a failing response. Two vascular events were reported, one recurrent TIA therefore classified as unrelated and one NSTEMI classified as possibly related to asciminib. Sixteen pts discontinued asciminib, mostly because of treatment failure (primary n=8, secondary n=2) or proceeding to SCT (n=5). Six out of 7 pts with AP/BC discontinued asciminib within 6 months because of treatment failure/SCT. The CI of maintaining or reaching CCYR/MR2.0 and MMR by 6 months for CP pts were 60% and 44%, respectively. Of note, only one out of 10 pts in CP with primary ponatinib-failure reached MR2.0 and none of these patients reached MMR. However, CP pts with secondary ponatinib-failure responded well with CCYR/MR2.0 or better in 78% (7/9). During asciminib treatment 5 pts progressed to advanced stage disease, 9 pts eventually underwent SCT and 7 pts died of whom 6 with a CML-related cause. Overall survival and EFS were 87% and 72%, with a median follow-up time of 10 and 8 months, respectively. Image:Summary/Conclusion: Our results show that asciminib is a well-tolerated novel treatment option for CML with adequate response rates, even in a heavily pretreated multi-resistant patient cohort. Most frequently reported AEs were manageable cytopenia and folliculitis. No patient discontinued asciminib solely due to intolerance. The CI of maintaining or reaching MR2.0/CCYR at 12 months was 57%. In our cohort, prior primary ponatinib-failure generally heralded subsequent asciminib treatment failure, both in the presence and absence of a T315I-mutation.